HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer

BMC Medical Genetics

Research Article

Lynley Ward¹  John P. Walsh²  Alexia L. Weeks²  Scott G. Wilson³  Jack Goldblatt⁴  Jennie Hui⁵ 

[1] Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, 6009, Nedlands, WA, Australia;Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, 6009, Nedlands, WA, Australia;School of Medicine & Pharmacology, The University of Western Australia, 6009, Crawley, WA, Australia;Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, 6009, Nedlands, WA, Australia;School of Medicine & Pharmacology, The University of Western Australia, 6009, Crawley, WA, Australia;Department of Twin Research and Genetic Epidemiology, King’s College London, SE1 7EH, London, UK;Genetic Services of Western Australia, King Edward Memorial Hospital, 6008, Subiaco, WA, Australia;School of Paediatrics and Child Health, The University of Western Australia, 6009, Crawley, WA, Australia;Pathwest Laboratory Medicine WA, 6009, Nedlands, WA, Australia;School of Pathology and Laboratory Medicine, University of Western Australia, 6009, Crawley, WA, Australia;

关键词: Papillary thyroid cancer;    Thyroid carcinoma;    Oncogenes;    HABP2;   

DOI  :  10.1186/s12881-016-0323-1

 received in 2015-12-18, accepted in 2016-06-23,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe genetic basis of nonsyndromic familial nonmedullary thyroid cancer (FNMTC) is poorly understood. A recent study identified HABP2 as a tumor suppressor gene and identified a germline variant (G534E) in an extended FNMTC kindred. The relevance of this to other FNMTC kindreds is uncertain.MethodsSanger sequencing was performed on peripheral blood DNA from probands from 37 Australian FNMTC kindreds to detect the G534E variant. Whole exome data from 59 participants from 20 kindreds were examined for mutations in HABP2 and the thyroid cancer susceptibility genes SRGAP1, NKX2-1, SRRM2 and FOXE1. The population prevalence of the G534E variant in HABP2 was examined in two independent cohorts.ResultsHeterozygosity for the G534E variant in HABP2 was found in 1 of 37 probands (2.7 %), but did not cosegregate with disease in this kindred, being absent in the proband’s affected sister. From whole exome data, pathogenic mutations were not identified in HABP2, SRGAP1, NKX2-1, SRRM2 or FOXE1. Heterozygosity for the G534E variant in HABP2 was present in 7.6 % of Busselton Health Study participants (N = 4634, unknown disease status) and 9.3 % of TwinsUK participants (N = 1195, no history of thyroid cancer).ConclusionsThe G534E variant in HABP2 does not account for the familial nature of NMTC in Australian kindreds, and is common in the general population. Further research is required to elucidate the genetic basis of nonsyndromic FNMTC.

【 授权许可】

CC BY   
© The Author(s). 2016